دورية أكاديمية
Folate binding protein: therapeutic natural nanotechnology for folic acid, methotrexate, and leucovorin.
| العنوان: | Folate binding protein: therapeutic natural nanotechnology for folic acid, methotrexate, and leucovorin. |
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| المؤلفون: | Merzel RL; Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA. mbanasza@umich.edu., Boutom SM; Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA. mbanasza@umich.edu., Chen J; Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA. mbanasza@umich.edu., Frey C; Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA. mbanasza@umich.edu., Shedden K; Department of Statistics, University of Michigan, Ann Arbor, Michigan 48109, USA., Marsh EN; Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA. mbanasza@umich.edu and Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA., Banaszak Holl MM; Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA. mbanasza@umich.edu and Department of Biomedical Science and Engineering, University of Michigan, Ann Arbor, Michigan 48109, USA and Program in Macromolecular Science and Engineering, University of Michigan, Ann Arbor, Michigan 48109, USA. |
| المصدر: | Nanoscale [Nanoscale] 2017 Feb 16; Vol. 9 (7), pp. 2603-2615. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: RSC Pub Country of Publication: England NLM ID: 101525249 Publication Model: Print Cited Medium: Internet ISSN: 2040-3372 (Electronic) Linking ISSN: 20403364 NLM ISO Abbreviation: Nanoscale Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Cambridge, UK : RSC Pub. |
| مواضيع طبية MeSH: | Drug Delivery Systems* , Nanoparticles*, Folate Receptor 1/*chemistry , Folic Acid/*administration & dosage , Leucovorin/*administration & dosage , Methotrexate/*administration & dosage, Humans ; Tissue Distribution |
| مستخلص: | Blood serum proteins play a critical role in the transport, biodistribution, and efficacy of systemically-delivered therapeutics. Here, we have investigated the concentration- and ligand-dependent aggregation of folate binding protein (FBP), focusing in particular on folic acid, an important vitamin and targeting agent; methotrexate, an antifolate drug used to treat cancer and rheumatoid arthritis; and leucovorin which is used to decrease methotrexate toxicity. We employed atomic force microscopy to characterize, on a particle-by-particle basis, the volumes of the FBP nanoparticles that form upon ligand binding. We measured the distribution of FBP nanoparticle volumes as a function of ligand concentration over physiologically- and therapeutically-relevant ranges. At physiologically-relevant concentrations, significant differences in particle volume distributions exist that we hypothesize are consistent with different trafficking mechanisms for folic acid and methotrexate. In addition, we hypothesize leucovorin is trafficked and delivered like folic acid at therapeutically-relevant concentrations. We propose that changes in dosing procedures could improve the delivery and therapeutic index for methotrexate and other folic acid-targeted drug conjugates and imaging agents. Specifically, we suggest pre-binding the drugs to FBP may provide a better formulation for drug delivery of methotrexate for both cancer and rheumatoid arthritis. This would be analogous to pre-binding paclitaxel to albumin, which is already used in the clinic. |
| المشرفين على المادة: | 0 (Folate Receptor 1) 935E97BOY8 (Folic Acid) Q573I9DVLP (Leucovorin) YL5FZ2Y5U1 (Methotrexate) |
| تواريخ الأحداث: | Date Created: 20170204 Date Completed: 20181030 Latest Revision: 20181030 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1039/c6nr09060e |
| PMID: | 28155935 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2040-3372 |
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| DOI: | 10.1039/c6nr09060e |